Expedient syntheses of N-heterocycles via intermolecular amphoteric diamination of allenes

Saturated 1,4-diazo heterocycles including piperazines, 1,4-diazepanes, and 1,4-diazocanes, are highly important for therapeutic development, but their syntheses are often tedious. We describe here an amphoteric diamination strategy to unite readily available 1,2-, 1,3- or 1,4-diamine derivatives with electron-deficient allenes via a formal [n + 2] (n = 4, 5, 6) cyclization mode to produce the corresponding 1,4-diazo heterocycles in just one step. This strategy features mild reaction conditions, high functional group tolerance, and scalability (gram scale). The reagents used are cheap and readily available and no transition metal catalysts are needed. More sophisticated products containing trifluoromethyl group or bicyclic ring systems can be accessed via a one-pot procedure as well. Our mechanistic studies support that formation of mono-iodinated or chlorinated diamine intermediates is important for the desired transformation and the commonly proposed chloride-iodide exchange process and a radical N−C bond formation is unlikely when the combination of NCS/KI is used.